Session: MON 758-775-Beta Cells, Glucose Control & Complications
Poster Board MON-767
Advanced Glycation End-products (AGEs), the highly reactive products of non-enzymatic glycation of proteins, lipids and nucleic acids, contribute to endothelial dysfunction, atherosclerosis and vascular injury under both normal and diabetic conditions.
The aim of the present study was to investigate the effect of AGEs in regulation of LOX gene/protein expression in human endothelial cells and to explore the potential functional impact of this interaction in an animal model.
Methods: Human aortic endothelial cells (HAECs) were treated with increasing concentrations (100, 200 μg/ml) of unmodified or glycated-bovine serum albumin (AGE-BSA) for different periods of time (24, 48, 72 h). LOX and receptor for AGE (RAGE) expression in HAECS was assessed by quantitative real-time polymerase chain reaction (real-time PCR) and flow cytometry. The binding capacity of AGE-induced transcription factors Nuclear Factor-κΒ (NF-κΒ) and Activator Protein-1 (AP-1) was monitored by electrophoretic mobility-shift assay (EMSA).
Aortic endothelium of normal rats fed with low- or high-AGE content diet for three months was further investigated for AGE, RAGE and LOX expression as well as further morphological alterations.
Main results: Treatment of HAECs with AGE-BSA triggered LOX transcription and protein expression in a time- and dose-dependent manner. This induction was mediated by activation and binding of NF-κΒ and AP-1 transcription factors to LOX gene promoter. Significantly increased expression of ΑGEs, RAGE and LOX was observed in the aortic endothelium of normal rats fed with high-AGE diet compared to controls.
Conclusions: Our data support the regulation of LOX gene by the AGE-induced transcription factors NF-κΒ and AP-1 in endothelial cells. Upregulation of LOX expression in endothelium constitutes a potential mechanism for compromised ECM integrity and function that characterizes microvascular complications associated with metabolic diseases and aging.
Nothing to Disclose: CA, CP, PK, GD, AS, ANG, EAK, AGP
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